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01.
arXiv (CS.CV) 2026-06-16

VANDERER: Map-Free Exploration using Future-Aware and Visual-Curiosity-Guided Diffusion Policy

Mobile agents require efficient exploration strategies to map unseen environments and autonomously plan tasks. Traditional methods rely on generating occupancy maps and optimizing the sequence in which unexplored regions are visited. However, in sensor-constrained settings, such as those limited to monocular cameras, generating accurate occupancy maps is challenging. To address this, we propose VANDERER, an exploration framework that leverages a Visual Curiosity Module (VCM) to guide pre-trained diffusion policies using only monocular image data. This curiosity module predicts the outcomes of proposed actions via a navigation world model and evaluates them through a curiosity cost. The cost then guides the diffusion process toward generating actions that maximize exploration. Evaluated across diverse simulated environments, VANDERER consistently outperforms established baselines, exploring an average of 13.4% more area than NoMaD. Our results reveal a direct correlation between visual and geometric curiosity in outdoor environments, demonstrating that VANDERER can effectively leverage this relationship for efficient exploration using sensor-constrained agents.

02.
arXiv (CS.LG) 2026-06-16

Generative Molecular Design with Steerable and Granular Synthesizability Control

arXiv:2505.08774v2 Announce Type: replace-cross Abstract: Designing molecules that are both property-optimal and readily synthesizable is a central challenge in drug discovery. Existing works that do consider synthesizability can jointly output predicted synthesis routes for generated molecules. However, there has been minimal attention in addressing the ease of synthesis and with flexibility to incorporate desired reaction constraints. On the other hand, virtual screening searches for commercially available compounds, but imposes challenges when scaling to ultra-large (billion-size and beyond) chemical spaces. Here, we propose a generative design framework that unifies synthesis-constrained molecular design and ultra-large-scale virtual screening through steerable and granular synthesizability control. Generated molecules satisfy arbitrary multi-parameter optimization objectives with predicted synthesis routes satisfying mix-and-match constraints: including or avoiding certain reactions, incorporating specific building blocks, and minimizing synthesis route length. In an end-to-end in-house campaign targeting BRD4, we designed molecules synthesizable with specific selected reactions and building blocks, synthesized all six selected compounds, and identified two micromolar binders. We further demonstrate that reaction control enables efficient navigation of ultra-large make-on-demand chemical spaces to identify property-optimal candidates. By applying our framework to Chemspace's Freedom 4.0 make-on-demand space (142 billion molecules), we generated ~320k molecules (0.00023% of the library) on a single consumer-grade GPU (with only 8 GB GPU memory) and identified a micromolar Wee1 binder amongst 60 synthesized candidates. The single unified framework thus enables generating novel synthesizable molecules and retrieving catalogue-ready candidates, offering a flexible solution to mitigating the synthesizability bottleneck.

03.
arXiv (CS.CL) 2026-06-17

When Multiple Scripts Matter: Evaluating ASR in Clinical Settings

Automatic speech recognition (ASR) in non-English clinical settings is challenged by multiscript variability, where the same term may appear in multiple valid orthographic forms. Conventional string-matching evaluation metrics often underestimate ASR performance by treating orthographic variants as errors. To address this issue, we introduce MultiClin, a clinical ASR benchmark designed to evaluate robustness to multiscript variability. Experiments across diverse ASR models show that multiscript-aware evaluation provides a fairer assessment of recognition quality than conventional single-reference evaluation. We further investigate the impact of script consistency during training and find that inconsistent script mappings increase orthographic uncertainty and hinder model convergence, with a balanced 50% mapping ratio producing the highest entropy. In contrast, script unification consistently yields the best ASR performance. Our dataset and code are publicly available at: https://github.com/aitrics-ronaldo/Interspeech_MultiClin.

04.
arXiv (CS.CL) 2026-06-19

Multi-Agent Transactive Memory

The decentralized deployment of LLM agents with diverse capabilities across diverse tasks motivates infrastructure for knowledge sharing across heterogeneous agent populations. Just as search engines index human-generated artifacts to support human problem solving, retrieval systems can organize agent-generated artifacts for reuse across agent populations. We extend retrieval-augmented generation - which demonstrates the value of human-authored artifacts to individual agents - to retrieval of agent-generated artifacts supporting a population of agents. In particular, agent trajectories encode reusable procedural knowledge, yet these artifacts are typically discarded after a single use or retained only by the producing agent, forcing newly instantiated agents to repeatedly rediscover existing solutions. We propose Multi-Agent Transactive Memory (MATM), a framework for population-level storage and retrieval of agent-generated trajectories, where producer agents contribute trajectories to a shared repository and consumer agents retrieve them to improve task execution. We focus on interactive environments (ALFWorld and WebArena), where trajectories are long and encode especially rich procedural structure. Our experiments demonstrate that retrieving trajectories from MATM improves downstream task performance and reduces interaction steps without coordination or joint training. These results position MATM as a design pattern for population-level experience sharing in open agent ecosystems.

05.
arXiv (CS.LG) 2026-06-12

Simplex-Constrained Sparse Bagging: Transitioning from Uniform Priors to Sparse Posteriors in Ensemble Learning

arXiv:2606.13589v1 Announce Type: new Abstract: We present Simplex-Constrained Sparse Bagging (SCSB), a mathematically rigorous framework for post-training compression and probability calibration of bootstrap-based bagging ensembles. Standard bagging ensembles (such as Random Forests, Bagged SVMs, and Bagged Neural Networks) assign uniform voting power to all constituent estimators. However, this naive uniform prior ignores the varying local competence of base estimators and contributes to model overconfidence. We formulate ensemble pruning and calibration as a joint optimization problem over the probability simplex by minimizing the Out-Of-Bag (OOB) loss. To induce sparsity, we address the theoretical "L1-simplex paradox" – the mathematical reality that the L1 norm is constant on the simplex and fails to prune – by introducing a concave quadratic penalty. SCSB is model-agnostic and achieves up to 96% ensemble compression, yielding linear inference speedups and superior probability calibration (lowered Expected Calibration Error) while preserving or enhancing generalization accuracy.

06.
arXiv (CS.AI) 2026-06-19

Overcoming Labelled Data Scarcity for Defect Classification in Scanning Tunneling Microscopy

arXiv:2506.01678v2 Announce Type: replace-cross Abstract: Scanning tunnelling microscopy (STM) is a powerful technique for imaging surfaces with atomic resolution, providing insight into physical and chemical processes at the level of single atoms and molecules. A regular task of STM image analysis is the identification and labelling of features of interest against a uniform background. Performing this manually is a labour-intensive task, requiring significant human effort. To reduce this burden, we propose an automated approach to the segmentation of STM images that uses both few-shot learning and unsupervised learning. Our technique offers greater flexibility compared to previous supervised methods; it removes the requirement for large manually annotated datasets and is thus easier to adapt to an unseen surface while still maintaining a high accuracy. We demonstrate the effectiveness of our approach by using it to recognise atomic features on three distinct surfaces: Si(001), Ge(001), and TiO$_2$(110), including adsorbed AsH$_3$ molecules on the silicon and germanium surfaces. Our model exhibits strong generalisation capabilities, and following initial training, can be adapted to unseen surfaces with as few as one additional labelled data point. This work is a significant step towards efficient and material-agnostic, automatic segmentation of STM images.

07.
arXiv (quant-ph) 2026-06-11

Implementing Hamiltonian Renormalization Group Flow on Quantum Computers with VAPOR

arXiv:2606.11306v1 Announce Type: cross Abstract: While Hamiltonian Lattice Gauge Theory is gaining traction, today's limited numerical capacity leaves simulations affected by discretization errors. This motivates the implementation of renormalization group (RG) techniques to find discretization-error-free operators. To this end, we introduce VAPOR, a variational quantum algorithm that decomposes operators into Pauli strings, identifies RG flow orbits, and determines fixed points of a naively discretized operator. We illustrate this using a toy model of a kinematic operator in a symmetry-restricted SU(2) Yang-Mills theory.

08.
arXiv (CS.AI) 2026-06-11

Tabular Foundation Models for Clinical Survival Analysis via Survival-Aware Adaptation

arXiv:2606.12006v1 Announce Type: cross Abstract: Predicting time-to-event outcomes such as mortality is a fundamental task in clinical decision-making, commonly addressed through survival analysis. While classical statistical and deep learning approaches have been widely studied, they typically require task-specific training and sufficient labeled data. Recent advances in tabular foundation models offer a new paradigm by learning general-purpose representations for structured data. However, their applicability to censored time-to-event prediction in clinical settings remains underexplored, as typical applications are restricted to discrete classification rather than survival analysis tasks. In this work, we propose a lightweight adaptation approach for applying tabular foundation models to clinical survival analysis by directly training a survival-aware head on top of the pretrained representations. We study representative architectures, including TabPFN, TabDPT, and TabICL, and adapt them using a multi-task logistic regression (MTLR) head to model right-censored time-to-event outcomes. We evaluate this approach on a diverse set of public survival benchmarks and two large-scale ICU cohorts, MIMIC-IV and eICU. Our results show that this transfer learning approach achieves competitive or superior performance compared to strong baselines. On MIMIC-IV, TabDPT-FT-MTLR reaches a C-index of 0.856, corresponding to a relative improvement of +1.4% over the best non-FM baseline (DeepSurv, 0.844) and +6.7% over the best zero-shot model (0.802). On eICU, TabICL-FT-MTLR achieves 0.797, yielding gains of +1.7% (DeepSurv, 0.784) and +6.4% (0.749), respectively. These findings highlight the importance of combining pretrained tabular representations with survival-aware objectives and suggest that tabular foundation models provide a practical and effective alternative for clinical survival prediction.

09.
arXiv (quant-ph) 2026-06-19

Thermodynamic Value of XOR-Game-Induced Side Information in a Szilard Engine

arXiv:2605.12044v3 Announce Type: replace Abstract: We introduce a Szilard-type thermodynamic valuation of side-information channels induced by Bell-type correlations. In each round, a two-level working system is thermalized with a degenerate Hamiltonian, so that its physical microstate is a uniform classical bit. A trusted referee embeds this bit into a finite two-player XOR game, and a correlation resource produces a compressed controller bit. The controller uses only this compressed bit as side information for feedback. The construction is formulated first for arbitrary finite XOR games. The referee encoding makes the game-winning event equivalent to correct prediction of the physical microstate. Consequently, the induced side-information channel is binary symmetric, with success probability equal to the XOR-game winning probability of the supplied behaviour. The reversible Szilard feedback value is therefore fixed by the mutual information between the microstate and the controller record. Optimizing over local, quantum, and nonsignalling behaviour sets turns the corresponding game values into local, quantum, and nonsignalling thermodynamic ceilings. The construction is an effective-channel valuation, not a claim that Bell nonlocality is thermodynamic fuel. The controller receives only the compressed prediction bit, not the auxiliary variables that define the game. The thermodynamic costs of the referee, the correlation resource, and the preprocessing are not included. When controller-memory reset is included in a full cycle, the net work is non-positive, consistently with the second law.

10.
arXiv (CS.LG) 2026-06-16

SDVDiag: Multimodal Causal Discovery for Online Diagnosis in Software-defined Vehicles

arXiv:2606.15559v1 Announce Type: cross Abstract: The transition toward software-defined vehicles concentrates an increasing share of vehicle functionality into distributed software services, where failures propagate through service dependencies and the surface symptom is often several causal hops away from the underlying defect. Existing approaches to causal root-cause analysis in such systems address this only partially: they typically reason over a single observability modality and operate in an offline, operator-driven mode that does not match the demands of continuous vehicle operation. This paper presents SDVDiag, a multimodal causal-discovery pipeline that fuses log-based and metric-based service representations into a shared embedding space before graph construction, coupled with an anomaly-driven trigger that converts the diagnostic platform from a manually operated batch tool into a continuously running online system. Evaluation on an Autonomous Valet Parking testbed shows that the multimodal pipeline produces sparser causal graphs than a metrics-only baseline (134 vs. 182 edges on average) and consistently outperforms it in edge-weighted reward against an expert knowledge graph at every stage of human-feedback refinement, showing a 2.4-fold improvement over the baseline after 60 feedback queries. An end-to-end fault-injection scenario further demonstrates that the integrated trigger correctly recovers a true root cause located two causal hops upstream of the observable symptom.

11.
arXiv (CS.AI) 2026-06-15

Regional Climate Model Emulation with Diffusion Approaches: What is the Added Value of Generative Machine Learning?

arXiv:2606.14570v1 Announce Type: cross Abstract: Emulators provide a cost-effective alternative to regional climate models (RCMs) by capturing their dynamical downscaling function. They link large-scale predictors simulated by global climate models (GCMs) to RCM-simulated high-resolution fields of the target variable, here precipitation. Machine learning methods, typically deep learning, are cheaper than running RCMs in computation time and energy. Among them, generative models are appealing because they can simulate ensembles of local high-resolution fields consistent with the predictors. This ensemble, which we call the uncertainty envelope, remains to be properly assessed for added value. Here, we make three contributions. First, we introduce ParamDiffusion, a new two-stage diffusion-based framework, and compare it with a state-of-the-art diffusion approach. Second, we expand standard validation through a comprehensive framework aligned with climate-science needs, examining specific precipitation events, including extremes. Third, within this framework, we assess the added value of diffusion approaches relative to deterministic methods. We intercompare four deep-learning models: a deterministic model designed to capture the precipitation tail; a parametric probabilistic model based on it; a recently proposed diffusion approach; and ParamDiffusion, which couples the parametric model with a diffusion model. Our results show that diffusion-based approaches reproduce climatological precipitation statistics with high skill, including distributional tails and spatially compounded extremes, while generating spatially detailed fields. However, none of the assessed models consistently accounts for the most extreme RCM-simulated events within its uncertainty envelope. Diffusion models are therefore promising for probabilistic RCM emulation, but progress is still required before they can reliably represent high-impact precipitation extremes.

12.
arXiv (CS.AI) 2026-06-16

AnonShield: Scalable On-Premise Pseudonymization for CSIRT Vulnerability Data

arXiv:2606.15650v1 Announce Type: cross Abstract: We present AnonShield, a high-throughput, on-premise pseudonymization system that combines GPU-accelerated NER, streaming processing, caching, and schema-aware configuration. Evaluated on datasets up to 550 MB (70,951 records), AnonShield reduces processing time from over 92 hours to under 10 minutes (up to 738x speedup) while achieving up to 94.2% F1-score and 96.7% recall. Our results show that scalable pseudonymization of vulnerability data is feasible without sacrificing analytical utility, enabling compliant data sharing in operational CSIRT environments.

13.
arXiv (CS.AI) 2026-06-16

The Reservoir Attention Network: Cross-Pass State in Pretrained Transformers via Content-Addressable Reservoir Injection

arXiv:2606.15678v1 Announce Type: cross Abstract: A feasibility and dynamics study of the Reservoir Attention Network (RAN), an architecture that injects a fixed, randomly-initialized reservoir into the mid-layer attention of a pretrained transformer to carry state across forward passes. Experiments span GPT-2 (124M, 355M) to Qwen2.5 (0.5B, 1.5B) on a single consumer GPU. The tasks are minimal probes chosen to isolate individual mechanisms; the broader always-alive agent vision is treated throughout as compute-limited future work, not a claim of this paper. The reservoir is left untrained (fixed random) by design: this isolates whether untrained recurrent dynamics alone suffice to carry usable cross-pass state, leaving trained recurrence as a complementary, more expensive direction.

14.
arXiv (CS.CL) 2026-06-16

JE-IRT: A Geometric Lens on LLM Abilities through Joint Embedding Item Response Theory

Standard LLM evaluation practices compress diverse abilities into single scores, obscuring their inherently multidimensional nature. We present JE-IRT, a geometric item-response framework that embeds both LLMs and questions in a shared space. For question embeddings, the direction encodes semantics and the norm encodes difficulty, while correctness on each question is determined by the geometric interaction between the model and question embeddings. This geometry replaces a global ranking of LLMs with topical specialization and enables smooth variation across related questions. Building on this framework, our experimental results reveal that out-of-distribution behavior can be explained through directional alignment, and that larger norms consistently indicate harder questions. Moreover, JE-IRT naturally supports generalization: once the space is learned, new LLMs are added by fitting a single embedding. The learned space further reveals an LLM-internal taxonomy that only partially aligns with human-defined subject categories. We also show that simple linear probes of the embedding space recover cross-subject ability directions, such as an arithmetic axis that highlights quantitatively demanding questions in seemingly distant subjects like virology and global facts. JE-IRT thus establishes a unified and interpretable geometric lens that connects LLM abilities with the structure of questions, offering a distinctive perspective on model evaluation and generalization.

15.
arXiv (CS.CV) 2026-06-18

SpectralDiT: Timestep-Conditioned Spectral Residual Correction for Flow-Matching DiTs

作者:

We propose SpectralDiT, a lightweight modification to flow-matching Diffusion Transformers that adds timestep-conditioned spectral correction to the MLP residual branch. The module decomposes each residual update into low- and high-frequency components on the patch-token grid, then learns a zero-initialized additive gate so the model initially matches the baseline DiT. On CIFAR-10 pixel-space generation, SpectralDiT improves FID from 20.78 to 19.71 at patch size 1 and reduces the radial Fourier spectrum gap. Furthermore, we scale our method to latent diffusion on ImageNet-100. With 0.6% additional theoretical FLOPs and 1.36% additional parameters, SpectralDiT improves latent flow-matching, achieving an 8.7% relative FID reduction under classifier-free guidance (CFG 2.0). All reported results are averaged over five seeds. Ablations and gate visualizations on CIFAR-10 reveal stable block-specific spectral correction patterns.

16.
arXiv (quant-ph) 2026-06-15

A Collective-Spin Derivation of the Uniform Magnon Hamiltonian in Cavity Magnonics

arXiv:2606.13830v1 Announce Type: cross Abstract: We present a direct collective-spin derivation of the effective uniform-mode Hamiltonian used in cavity magnonics. Starting from a nearest-neighbor Heisenberg ferromagnet coupled to long-wavelength magnetic fields, we show that the relevant dynamics can be restricted to the fully symmetric spin sector, where the exchange interaction contributes only a constant energy shift and the ferromagnet behaves as a macrospin of length $Ns$. Applying the Holstein–Primakoff transformation directly to this total spin yields the usual uniform magnon mode and its leading nonlinear corrections without first introducing site-resolved bosonic operators. This collective formulation makes explicit the interpretation of the ferromagnet as a synthetic large-spin atom and provides a compact route to the effective Hamiltonians used in driven and Floquet cavity magnonics. As a physical consequence, the leading nonlinear correction produces an occupation-dependent reduction of the effective magnon–photon coupling, providing a simple signature of finite-spin saturation under strong uniform-mode driving.

17.
medRxiv (Medicine) 2026-06-22

Impact of Antidiabetic Medications on IgG and Plasma Protein N-Glycosylation in Type 2 Diabetes Patients

Introduction. Diabetes is a growing global health challenge, necessitating effective management strategies. Glycosylation, a highly regulated post-translational protein modification, has emerged as a pivotal factor in diabetes pathophysiology. However, the modulation of protein glycosylation by antidiabetic treatment is still largely unknown. This study explored the longitudinal effects of four distinct antidiabetic therapies - metformin, insulin, sodium-glucose cotransporter-2 (SGLT2) inhibitors, and glucagon-like peptide-1 receptor agonists (GLP-1RA) - on plasma protein and immunoglobulin G (IgG) glycosylation in patients with type 2 diabetes (T2D). Research Design and Methods. Plasma protein and IgG N-glycans were enzymatically released, purified and chromatographically profiled in a cohort of 124 patients, examined at four time points, to assess therapy-induced glycan alterations. Linear mixed models adjusting for covariates and multiple testing (FDR

18.
medRxiv (Medicine) 2026-06-22

Body composition subphenotypes, cardiometabolic risk and incident outcomes: validation in the population-based NAKO and UK Biobank imaging cohorts

Background Anthropometric measures do not adequately capture heterogeneity in body fat distribution and corresponding cardiometabolic risk, whereas magnetic resonance imaging (MRI) enables precise differentiation and quantification of adipose tissue compartments and ectopic fat. We aimed to validate previously derived MRI-based body composition subphenotypes and their cardiometabolic risk profiles in two independent European cohorts. Methods Using deep learning-based image analysis, we quantified bone marrow, visceral, subcutaneous, cardiac, renal sinus, hepatic, skeletal muscle, and pancreatic fat in the imaging substudies of two population-based cohorts: the German National Cohort (NAKO, N=29,314, age range 19-74 years) and the UK Biobank (N=36,109, age range 40-69 years). Body composition subphenotypes, previously identified by k-means clustering, were evaluated using a rigorous statistical cluster validation framework with method-based and results-based approaches. In NAKO, cross-sectional associations between subphenotypes and estimated cardiovascular disease risk scores were examined using linear regression. In UK Biobank, longitudinal associations between subphenotypes and incident cardiometabolic outcomes, ascertained through hospital record linkage, were analysed using Cox regression. Findings All five body composition subphenotypes were robustly validated across both cohorts, and showed distinct fat distribution patterns and cardiometabolic risk profiles: I "lean", II "average adiposity", III "bone and muscle adiposity", IV "hepato-abdominal adiposity", and V "general and pancreatic adiposity". Subphenotypes I-III showed progressive adipose tissue remodelling patterns likely reflecting ageing trajectories. The "hepato-abdominal adiposity" subphenotype showed highest risk of incident diabetes, whereas the "general and pancreatic adiposity" subphenotype showed highest overall cardiovascular disease burden and metabolic impairment. Interpretation MRI-derived body composition subphenotypes represent distinct fat distribution patterns that reflect ageing- and disease-related processes, which supports the potential of body composition phenotyping for improved cardiometabolic risk stratification and targeted prevention.

19.
arXiv (CS.AI) 2026-06-17

Catastrophic Forgetting is Low-Rank: A Function-Space Theory for Continual Adaptation

arXiv:2606.18024v1 Announce Type: cross Abstract: Catastrophic forgetting in continual adaptation is usually studied through parameter drift, replay, or distillation, but these views do not identify which output-space directions are vulnerable. We give a function-space account in the NTK regime: new-task training induces old-task prediction drift through the cross-task kernel, yielding a closed-form predictor for the forgetting vector before any new-task gradient step. In frozen-backbone linear-head PEFT-CL, where the model is linear in the trainable parameters, the predictor is exact up to numerical precision; for nonlinear adapters/full fine-tuning, it is a local NTK approximation. The same expression reveals that forgetting concentrates in a small number of old-task NTK eigenmodes and under frozen linear heads gives a Kronecker scaling rule for the vulnerable rank. These results clarify the relation to prior NTK-overlap theory, explain why parameter-space regularizers can miss output-space interference, and motivate a targeted spectral regularizer.

20.
arXiv (CS.AI) 2026-06-16

Gated QKAN-FWP: Scalable Quantum-inspired Sequence Learning

arXiv:2605.06734v2 Announce Type: replace-cross Abstract: Fast Weight Programmers (FWPs) encode temporal dependencies through dynamically updated parameters rather than recurrent hidden states. Quantum FWPs (QFWPs) extend this idea with variational quantum circuits (VQCs), but existing implementations rely on multi-qubit architectures that are difficult to scale on noisy intermediate-scale quantum (NISQ) devices and expensive to simulate classically. We propose gated QKAN-FWP, a fast-weight framework that integrates FWP with Quantum-inspired Kolmogorov-Arnold Network (QKAN) using single-qubit data re-uploading circuits as learnable nonlinear activation, known as DatA Re-Uploading ActivatioN (DARUAN). We further introduce a scalar-gated fast-weight update rule that stabilizes parameter evolution, supported by a theoretical analysis of its adaptive memory kernel, geometric boundedness, and parallelizable gradient paths. We evaluate the framework across time-series benchmarks, MiniGrid reinforcement learning, and highlight real-world solar cycle forecasting as our main practical result. In the long-horizon setting with 528-month input window and 132-month forecast horizon, our 12.5k-parameter model achieves lower scaled Mean Square Error (MSE), peak amplitude error, and peak timing error than a suite of classical recurrent baselines with up to 13x more parameters, including Long Short-Term Memory (LSTM) networks (25.9k-89.1k parameters), WaveNet-LSTM (167k), Vanilla recurrent neural network (11.5k), and a Modified Echo State Network (132k). To validate NISQ compatibility, we further deploy the trained fast programmer on IonQ and IBM Quantum processors, recovering forecasting accuracy within 0.1% relative MSE of the noiseless simulator at 1024 shots. These results position gated QKAN-FWP as a scalable, parameter-efficient, and NISQ-compatible approach to quantum-inspired sequence modeling.

21.
bioRxiv (Bioinfo) 2026-06-14

Generative design of antigen-specific T-cell receptor sequences with a conditional diffusion model

T cell receptor (TCR)-based immunotherapy holds immense potential for treating cancers and infectious diseases, where highly antigen-specific TCR recognition is crucial for adaptive immunity against tumors and pathogens. Engineering or de novo generation of the complementarity-determining region 3 (CDR3) loops of TCRs using artificial intelligence offers a powerful alternative to designing reactive TCRs rather than laborious experimental screening. However, current in silico approaches are constrained by weak conditional guidance, limited flexibility, and a lack of rigorous functional validation. To address these limitations, we introduce TCRDiff, a generative diffusion framework for designing antigen-specific TCRs conditioned on peptide-MHC (pMHC) targets and germline-encoded variable genes. By leveraging pre-trained knowledge from massive T-cell repertoires and TCR-pMHC recognition data, TCRDiff generates CDR3{beta} sequences with state-of-the-art fidelity to native binding TCRs through a denoising diffusion process. Furthermore, incorporating the interface geometry features generated TCR-pMHC complexes with superior structural plausibility. As a proof of concept, we deployed TCRDiff in a systematic pipeline to design candidate TCRs for immunotherapy. In vitro activation assays validated that TCRDiff-generated TCRs specifically recognize the MAGE-A3 epitope with minimized off-target cross-reactivity. Together, TCRDiff establishes a powerful, validated computational paradigm to accelerate the development of TCR-based immunotherapies.

22.
bioRxiv (Bioinfo) 2026-06-18

Elucidating the Design Space of Generative Models for Single-Cell Perturbation Prediction

Next-token prediction has produced predictable scaling in language, but the recipe presumes a sequence of tokens with a meaningful order. Single-cell RNA-seq counts have no natural gene ordering, so applying the recipe directly to raw expression fails under an ill-suited left-to-right bias. We instead ask whether a learned latent can supply the structure the recipe needs. We introduce texttt{ExpressionVAE} (eVAE), a discrete-latent perturbation model that compresses each cell into a short sequence of discrete codes through a finite-scalar-quantization (FSQ) bottleneck and trains a perturbation-conditioned discrete prior over those codes. On Replogle and Parse~1M, eVAE sets a new state of the art on every distributional metric and leads on most cell-eval perturbation metrics, with Fr'echet distance and $mathrm{MMD}^2$ roughly $3$ to $20times$ lower than the strongest continuous-latent baseline. Swapping the prior between autoregressive and masked discrete diffusion leaves performance near-identical, isolating the gain to the discrete latent itself rather than the prior family. A decoder-head ablation then exposes a single design axis, the richness of the predictive distribution at inference, that splits the standard metrics into two groups, variance-sensitive and mean-sensitive, which move in opposite directions along the axis. Finally, on a held-out CRISPRi reversion benchmark of $1{,}732$ perturbations under inflammatory cytokine stress, the frozen eVAE encoder outperforms UMAP and differential expression and matches scGPT on perturbation ranking at a fraction of the data.

23.
arXiv (CS.CV) 2026-06-18

Semantic Robustness Certification for Vision-Language Models

Vision-language models (VLMs) are now widely used in downstream tasks. However, real-world applications often expose VLMs to distribution shifts induced by semantic variation (e.g., shape, size, and style). Robustness certification determines if a model's prediction changes when transformations are applied to its input. While most certification frameworks study geometric or pixel-level transformations over inputs, this work proposes a novel framework that enables certifying VLM robustness under semantic-level transformations. Leveraging the open-vocabulary capability of VLMs, we use text prompts as semantic proxies to construct transformations parameterized by an extent that controls the degree of semantic variation. By characterizing the VLM decision boundary in closed form, our framework quantitatively certifies extent intervals for which the predicted class remains unchanged under the semantic transformation. Our framework is the first to certify VLM robustness under semantic-level variations without requiring additional data for each variation, making it practical to apply. Experiments on both synthetic and real-world data show that our framework enables certifying robustness under diverse semantic variations across scenarios.

24.
bioRxiv (Bioinfo) 2026-06-18

A unified smoothing framework for protein domain bigram model

Biomolecular sequences can be represented as strings over an alphabet, an analogy that has motivated many applications of computational linguistic techniques to biological problems. However, such methods must be adapted to the characteristic scale and organization of biomolecular data. Here, we consider the problem of bigram smoothing for multidomain protein architectures, where domain bigram frequency data is extremely sparse and differs from textual data in alphabet size, string length distribution, the relationship between bigram and unigram frequencies, tandem repeat lengths, and the distribution of domain adjacencies. Moreover, some domain combinations are unobserved because they are biologically incompatible, others because the data are incomplete. A smoothing method that distinguishes these two cases is required. We propose a unified smoothing framework based on interpolation that can be tuned to accommodate different bigram data characteristics. Within this framework, we design specific model variants suited to protein domain bigram data: these assign low adjusted counts to pairs that are likely incompatible, while making appropriate adjustments for undersampled pairs. We demonstrate empirically that this approach distinguishes the two cases while preserving the characteristic signatures of multidomain data.

25.
arXiv (CS.LG) 2026-06-17

Manifold GCN: Diffusion-based Convolutional Neural Network for Manifold-valued Graphs

arXiv:2401.14381v3 Announce Type: replace Abstract: We propose two graph neural network layers for graphs with features in a Riemannian manifold. First, based on a manifold-valued graph diffusion equation, we construct a diffusion layer that can be applied to an arbitrary number of nodes and graph connectivity patterns. Second, we model a tangent multilayer perceptron by transferring ideas from the vector neuron framework to our general setting. Both layers are equivariant under node permutations and the feature manifold's isometries. These properties have led to a beneficial inductive bias in many deep-learning tasks. Furthermore, they enable novel, more flexible feature designs. Numerical examples on synthetic data and an Alzheimer's classification application on triangle meshes of the right hippocampus demonstrate the usefulness of our new layers: While they apply to a much broader class of problems, they outperform task-specific state-of-the-art networks.